The goal of this project is to determine the relationship between Phosphoinositide 3-Kinase (PI3K) signaling and lymphocyte motility as well as in-vivo response to antigen. Specific aims will be addressed by capitalizing upon the multi-photon microscopy imaging techniques of secondary lymphoid tissues established by our research group. To test the hypothesis that functional PI3K signaling plays central role in lymphocyte motility, homing and the in-vivo immune response three specific aims are proposed; 1) Define the alterations in motility and homing of T and B lymphocytes after treatment with the covalent PI3K inhibitor wortmannin, 2) Establish the motility and homing kinetics of T and B lymphocytes isolated from PI3K knock-out mice that have been adoptively transferred into wild type mice, 3) Determine the effect of PI3K knock-out and wortmannin on the immune response in the living lymph node. [unreadable] [unreadable] [unreadable]